INEU.posters

Functional validation of the PSEN1 R358P and PSEN1 T119I variants in Alzheimer's Disease: an in vitro study

Tue, 23 Dec 2025 00:00:00 GMT

Functional validation of the PSEN1 R358P and PSEN1 T119I variants in Alzheimer's Disease: an in vitro study García Chialva, Diego; Cifarelli, Diego; Isaja, Luciana; Apecetche, Manuela; Martínes Ojeda, Laura; Itzcovich, Tatiana; Chrem Méndez, Patricio Alexis; Sevlever, Gustavo Emilio; Scassa, Maria; Surace, Ezequiel Ignacio; Romorini, Leonardo Background Alzheimer's disease (AD) is a neurodegenerative disorder and the leading cause of dementia worldwide. It is characterized by progressive neuronal degeneration and the accumulation of beta‐amyloid plaques (Aβ) and neurofibrillary tangles (NFT) in the brain. AD manifests in sporadic AD (sAD) and familial AD (fAD). fAD is associated with inherited genetic mutations affecting amyloid precursor protein (APP) processing, involving genes such as APP, PSEN1, and PSEN2. Method The identification of two novel PSEN1 variants, p.T119I and p.R358P in early‐onset AD patients at FLENI provided a unique opportunity to study their possible implications in fAD. Notably, the patient harboring the PSEN1 R358P variant also carried a novel SORL1 variant (Gly1536Asp). Noteworthy, genetic variants in SORL1 are now considered a major AD risk factor. To evaluate the role of these two novel PSEN1 variants in APP processing, we developed a cellular model using PSEN1 Knock‐Out (KO) HEK293T cells created through CRISPR/Cas9 technology. We assessed the Aβ 42 /Aβ 40 ratio (AD biomarker) in the supernatant of PSEN1 KO‐cells transfected with expression vectors coding for APP and either wild‐type PSEN1, the novel PSEN1 variants or PSEN1 A246E (a known pathogenic mutation). Result We observed a significant (p <0.05) increase in the Aβ 42 /Aβ 40 ratio in HEK293T cells transfected with PSEN1 A246E or PSEN1 R358P plasmids and a slight trend towards an increase in cells transfected with PSEN1 T119I vector. In the case of PSEN1 R358P‐transfected cells, the increase in the Aβ 42 /Aβ 40 ratio observed was primarily due to the decrease in Aβ 40 levels in the supernatant. Conclusion These findings suggest a potential pathogenic role for the PSEN1 R358P variant in fAD, independent of the co‐occurring SORL1 mutation.

A RoadMap for Neuropsychological Assessment of the Right Temporal Variant of Frontotemporal Dementia (rtvFTD): Case Studies and Practical Applications

Wed, 01 Jan 2025 00:00:00 GMT

A RoadMap for Neuropsychological Assessment of the Right Temporal Variant of Frontotemporal Dementia (rtvFTD): Case Studies and Practical Applications De Los Santos, Loana; Morello García, Florentina; Ardohain Cristalli, Carolina Agata; Tabernero, María Eugenia; Clarens, María Florencia; Crivelli, Lucía; Magrath Guimet, Nahuel Background: The right temporal variant of frontotemporal dementia (rtvFTD) is a neurodegenerative condition characterized by progressive atrophy of the right anterior temporal lobe (rATL), significantly impairing semantic-pragmatic comprehension and social cognition. In Latin America, although magnetic resonance imaging (MRI) and computed tomography (CT) are widely available, there is still a need for neuropsychological tools to assess cognitive and social changes in rtvFTD. Currently, this condition remains a subject of debate due to diagnostic challenges stemming from a lack of consensus in terminology and variability in assessment tools (Ulugut et al., 2024; Younes et al., 2022). The aim of this study is to propose neuropsychological tools to characterize both the profile and cognitive changes of rtvFTD and present a structured roadmap to help differentiate rtvFTD from other dementias. Additionally, this roadmap contributes to the design of personalized therapeutic interventions. Method: Two clinical cases diagnosed with rtvFTD at FLENI (Buenos Aires, Argentina) were studied. Both patients underwent standard neuropsychological evaluations focused on semantic-pragmatic language and social cognition, using locally adapted tests for naming, semantic verbal fluency, semantic association, prosody, pragmatics, and speech intentionality. Findings were correlated with MRI scans to validate the proposed roadmap. Result: The patients exhibited severe deficits in naming, semantic verbal fluency, semantic-pragmatic impairments, and alterations in emotional prosody, theory ofmind, and facial emotion recognition. Executive attentional systems, visuospatial abilities, and memory remained preserved. These findings aligned with patterns of atrophy and hypometabolism observed in the rATL and were consistent with current literature on the neuropsychological and clinical profiles of the rtvFTD. Figure 1 shows the proposed neuropsychological assessment approach, using a regionally adapted cognitive battery designed to capture rtvFTD symptoms in Spanish-speaking populations and to guide differentiation from other dementia variants. Conclusion: This roadmap provides a practical guide that includes neuropsychological tests for the assessment of rtvFTD, particularly in Spanish-speaking countries. By integrating evaluations targeting semantic-pragmatic language and social cognition, the roadmap allows for precise differentiation of rtvFTD from other frontotemporal dementia variants. Furthermore, it contributes to the development of personalized therapeutic interventions, aiming to improve patient quality of life and support clinical practices in Spanish-speaking regions.

LatAm Fingers Initiative: Bringing Diversity Upfront

Thu, 01 Dec 2022 00:00:00 GMT

LatAm Fingers Initiative: Bringing Diversity Upfront Crivelli, Lucía

LatAm Fingers Initiative: Challenges and opportunities of launching amulticultural trial in pandemic times

Tue, 20 Dec 2022 00:00:00 GMT

LatAm Fingers Initiative: Challenges and opportunities of launching amulticultural trial in pandemic times Calandri, Ismael Luis; Crivelli, Lucía; Caramelli, Paulo; Lopera, Francisco; Nitrini, Ricardo; Sosa, Ana Luisa; Salinas Contreras, Rosa María; Suemoto, Claudia Kimie; Velilla, Lina M.; Sanches Yassuda, Mónica; Sevlever, Gustavo Emilio; Allegri, Ricardo Francisco; LatAm FINGERS